neoadjuvant ipilimumab/nivolumab for patients with recurrent, high risk, resectable melanoma

Conditions: Melanoma

Summary: the goal of this clinical trial is to study the impact of neoadjuvant ipilimumab and nivolumab for melanoma patients that had recurrence during or after adjuvant anti-pd-1 therapy. participants will receive 2 cycles of treatment prior to their standard of care surgery. after surgery participants will receive standard of care adjuvant therapy and be followed for response.


Eligibility criteria:
inclusion criteria: * subjects aged ≥ 18 years. * histologically confirmed stage iiib-d or stage iv recurrent metastatic melanoma that is resectable or borderline resectable as determined by a surgical oncologist. * recurrent disease at eligibility must have been confirmed with biopsy while receiving or within 3 months of completion of adjuvant anti-pd1 therapy. * ecog performance status ≤ 1. * adequate organ function as defined as: * hematologic: * absolute neutrophil count (anc) ≥ 1500/mm3 * platelet count ≥ 100,000/mm3 * hemoglobin ≥ 10 g/dl * hepatic: * total bilirubin ≤ 1.5x institutional upper limit of normal (uln) * ast(sgot)/alt(sgpt) ≤ 3 × institutional uln ----subjects with liver metastases will be allowed to enroll with ast and alt levels ≤ 5 x uln. * renal: * estimated creatinine clearance ≥ 50 ml/min by cockcroft-gault formula: * for subjects of childbearing potential: negative pregnancy test or evidence of post-menopausal status or evidence of permanent surgical sterilization. the post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. the following age-specific requirements apply: * subjects \< 50 years of age: * amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and * luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution * subjects ≥ 50 years of age: * amenorrheic for ≥ 12 months following cessation of all exogenous hormonal treatments; or * had radiation-induced menopause with last menses \>1 year ago; or * had chemotherapy-induced menopause with last menses \>1 year ago * subjects of childbearing potential and subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception as described in section 5.3.1. * subject has adequate archival tissue or agrees to undergo a fresh tissue biopsy if sufficient archival tissue is unavailable. * recovery to baseline or ≤ grade 1 ctcae v5 from toxicities related to any prior treatments, unless ae(s) are clinically nonsignificant and/or stable on supportive therapy per the treating investigator. * able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. exclusion criteria: * receiving other investigational agents currently or within 28 days of study treatment. * prior systemic anti-cancer therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter. * prior radiotherapy 45 days prior to the first dose of study treatment. * major surgery 4 weeks prior to starting study drug or who have not fully recovered from major surgery. * active infection requiring the use of systemic antibiotics. * systemic steroid therapy greater than physiologic equivalent (10mg prednisone/day) or any other form of systemic immunosuppressive therapy within 7 days prior to registration. * active secondary malignancy, unless the malignancy is not expected to interfere with the evaluation of safety * known brain metastases or cranial epidural disease. * current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions: --cardiovascular disorders: * congestive heart failure new york heart association class iii or iv, unstable angina pectoris, serious cardiac arrhythmias. * stroke (including transient ischemic attack \[tia\]), myocardial infarction (mi), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before the first dose. * qtc prolongation defined as a qtcf \> 500 ms. * known congenital long qt. * left ventricular ejection fraction \< 55%. * uncontrolled hypertension defined as ≥ 140/90 as assessed from the mean of three consecutive blood pressure measurements taken over 10 minutes. * any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/psychological issues, etc.) * hiv infection with a detectable viral load within 6 months of the anticipated start of treatment. --note: subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial. * active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and tb testing in line with local practice), hepatitis b (positive hbv surface antigen (hbsag) result), or hepatitis c. --note: subjects with a past or resolved hbv infection (defined as the presence of hepatitis b core antibody \[anti-hbc\] and absence of hbsag) are eligible. subjects positive for hepatitis c (hcv) antibody are eligible only if polymerase chain reaction is negative for hcv rna. * medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study. * known prior severe hypersensitivity to investigational product (ip) or any component in its formulations (nci ctcae v5.0 grade ≥ 3). * subjects taking prohibited medications as described in section 6.7.2. a washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.